In the case of external preparations for treatment of superficial mycoses, their therapeutic effect is greatly influenced by each drug's ability to permeate the skin and nail. Particularly in the treatment of onychomycoses, oral antifungal preparations are mainly used because existing antifungal preparations for external use cannot achieve sufficient drug permeation into the thick keratin layer in the nail plate and hence cannot produce any antifungal effect on fungi in the nail. However, treatment via the oral route requires 3 to 6 months in terms of nail turnover. For this reason, there appear side effects such as digestive symptoms and/or hepatic dysfunction, and it is recommended to receive periodic examinations of liver function and blood during the treatment. This significantly reduces the compliance of patients.
On the other hand, the applicant has designed an antifungal compound, (2R,3R)-2-(2,4-difluorophenyl)-3-(4-methylenepiperidin-1-yl)-1-(1H-1,2,4-triazol-1-yl)-butan-2-ol (Patent Document 1). The applicant has also elucidated that KP-103 solutions (in 74% polyethylene glycol/25% ethanol) exert a therapeutic effect on onychomycoses (tinea unguium in guinea pigs), which was not achieved by conventional antifungal preparations for external use (Patent Document 2). In light of onychomycosis treatment, there has been a demand for the development of KP-103 preparations showing a higher curing effect than KP-103 solutions, wherein the preparations allow increased area and/or speed of absorption/permeation into the nails of fingers and toes, particularly into deformed nails, and thereby produce a curing effect within a short period of time. However, such external preparations for superficial mycoses with enhanced permeation have been difficult to develop. Particularly in the case of external preparations for onychomycoses, the same permeation effect as observed in the skin cannot apply to the nail because of differences in chemical structure between nail and skin. Thus, it has been difficult to improve drug permeation in the nail.
Patent Document 1: Japanese Patent No. 2768830
Patent Document 2: International Patent Publication No. WO01/07643